Catheter system and method for injection of a liquid embolic composition and a solidification agent

ABSTRACT

A catheter according to the present invention includes a multiple lumen catheter for delivery of a liquid embolic composition through a first lumen and delivery of a solidification agent through a second lumen. The catheter allows adjustment of the relative longitudinal position of the two lumens to control the solidification of the embolic composition within a blood vessel. The multiple lumen catheter system is used by inserting the catheter endovascularly into an aneurysm site and injecting a liquid embolic composition through the first lumen while injecting a solidification agent through the second lumen to wash the area of the aneurysm of blood which has become saturated with solvent, while replacing it with a fresh solidification agent. The controlled solidification of the liquid embolic composition by use of the solidification agent allows the aneurysm to be filled precisely and rapidly even when the aneurysm is located such that gravity does not cause the liquid embolic composition to flow into the aneurysm.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The invention relates to a catheter system and method forcombined injection of a liquid embolic composition and an embolicsolidification agent, and more particularly, to a catheter systemincluding a multiple lumen catheter for injection of a liquid emboliccomposition through a first lumen and an embolic solidification agentthrough a second lumen. The catheter system is used for delivery of theembolic composition in a controlled manner for embolizing blood vessels.

[0003] 2. State of the Art

[0004] In many clinical situations it is desirable to selectivelyocclude blood vessels for a variety of purposes, such as, the control orprevention of bleeding, the prevention of blood supply to tumors, andthe blocking of blood flow within an aneurysm. Embolization of bloodvessels has been performed by employing certain polymer compositionsand/or particulate including silicone balloons, metallic coils, PAparticles, gelatin,. sclerosing material, and the like, to selectivelyblock blood flow in the blood vessels.

[0005] Intracranial aneurysms are present in between one and ninepercent of the population and rupture at a rate of more than 50,000 peryear in North America. Intracranial aneurysms are abnormal blood filleddilations of a blood vessel wall which may rupture causing significantbleeding and damage to surrounding brain tissue or death. Traditionally,intracranial aneurysms have been surgically clipped to reduce the riskof rupture by placing a metal clip around the neck of the aneurysm tocut off and prevent further blood flow to the aneurysm. However, manyaneurysms cannot be treated surgically because of either the locationand configuration of the aneurysm or because the condition of thepatient does not permit cranial surgery.

[0006] When aneurysms cannot be treated surgically or when surgery isconsidered to be too risky or invasive, aneurysms may be treatedendovascularly with coils. The coils are placed in the aneurysm byextending a catheter endovascularly to the site of the aneurysm andpassing single or often multiple platinum or tungsten coils through thecatheter into the aneurysm. The coils placed within the aneurysm createa thrombus which occludes the aneurysm and prevents further blood flowto the aneurysm. The treatment of intracranial aneurysms with coilsisolates the aneurysm from arterial circulation helping to guard againstrupture and further growth of the aneurysm. However, the use of platinumcoils to treat intracranial aneurysms may not be a permanent solutionbecause the blood clot around the coils may declot or dissolve due tothe dynamic nature of the blood clotting function. Once a clot formedaround the coils in an aneurysm declots, the coil can no longer performits function of occluding the aneurysm. In addition, the coils maybecome dislodged and enter the patient's blood stream causing blockagesat other locations within the vascular system.

[0007] Another drawback associated with the use of coils to occlude ananeurysm is that the coils are known to compact over time leavingcavities for subsequent aneurysm growth. In addition, if a subsequentsurgical clipping procedure is warranted, it can be difficult to placethe clip over the coil mass.

[0008] Aneurysms having large necks are not easily treated by eithersurgical clipping or by coils because the aneurysm neck may have a shapewhich cannot be completely clipped surgically and the coils may tend tobecome dislodged from the aneurysm when the neck is particularly large.

[0009] One minimally invasive procedure for treating intracranialaneurysms which addresses the problems with the surgical clipping andcoil techniques involves the endovascular injection of a liquid emboliccomposition which solidifies in the aneurysm to occlude the aneurysm.The liquid embolic composition generally includes a water-insoluble,biocompatible polymer and a biocompatible solvent. Once the liquidembolic composition is injected into the aneurysm, the biocompatiblesolvent dissipates into the blood and the polymer solidifies to occludethe blood flow through the aneurysm.

[0010] Typically, liquid embolic compositions include a water insoluble,biocompatible, non-biodegradable polymer dissolved in a biocompatiblesolvent and preferably these compositions include a radiopaque materialwhich allows the physician to view the embolization procedure byfluoroscopy. Prior to delivery of the embolic composition to theaneurysm, the aneurysm and delivery device are preferably positioned sothat the liquid embolic composition will be delivered by gravity intothe aneurysm and will remain in the aneurysm (with the aneurysm neckpointing up). As the embolic composition is delivered to the aneurysm,the solvent dissipates from the polymer material causing the polymermaterial within the aneurysm to solidify.

[0011] Depending on the rate at which the liquid embolic material isinjected into the blood vessel and the amount of blood flow present, thepolymer may remain in liquid form for a period of time while the solventdissipates into the blood stream. Moreover, the solvent may not becompletely dissipated from a center of the polymer mass creating a masswith a solid outer shell and liquid interior. In addition, the solventconcentration at the point of injection may increase to a point wheresmall strings of unsolidified polymer material may separate from thepolymer mass and be carried away in the blood stream where it canocclude an undesired vascular location. Since the solvent generally hasa density greater than water or blood, gravity may hold the solvent inthe aneurysm and prevent the polymer from solidifying.

[0012] Accordingly, it would be desirable to provide a method forcontrolling the solidification of the polymer material during injection.It would also be desirable to provide a method for filling an aneurysmwhich is riot positioned such that gravity may be used to cause theembolic composition to flow into and remain in the aneurysm, since apatient's anatomical position cannot always be in a gravity dependentposition.

[0013] As disclosed in U.S. patent application Ser. No. 08/730,701,embolization of a blood vessel with a liquid embolic compositiongenerally includes a preparatory step of flushing a delivery catheterthrough which the liquid embolic composition is to be delivered with thebiocompatible solvent material to remove any aqueous material from thecatheter. The removal of any aqueous material from the catheter inhibitssolidification of the embolic composition within the catheter duringdelivery. This preliminary step of flushing with the solvent must bedone at a slow flow rate to prevent damage to the blood vessel caused byhigh concentrations of the solvent which can be toxic and may causevascular spasms. However, it would be desirable to be able to performthe preliminary flushing of the delivery catheter without concern ofcausing tissue damage.

SUMMARY OF THE INVENTION

[0014] According to one aspect of the invention a catheter system forcontrolled delivery of polymer compositions includes a multiple lumencatheter having a first lumen and a second lumen for delivery of fluid.A first fluid delivery port delivers fluid to the first lumen and aliquid supply is connected to the first fluid delivery port for deliveryof a liquid embolic composition through the first lumen. A second fluiddelivery port delivers fluid to the second lumen and a solidificationagent supply is connected to the second fluid delivery port for deliveryof a solidification agent through the second lumen to enhancesolidification of the liquid embolic composition delivered through thefirst lumen.

[0015] According to a further aspect of the invention a catheter forcontrolled delivery of embolic compositions includes a first tube formedof a DMSO compatible material, a second tube connected to the first tubeand an actuator for sliding the first tube longitudinally with respectto the second tube. A first fluid delivery port is connected to a lumenof the first tube for delivery of a liquid embolic composition includinga biocompatible, water insoluble, polymer composition dissolved in DMSO.A second fluid delivery port is connected to a lumen of the second tubefor delivery of a solidification agent which encourages dissipation ofthe DMSO and solidification of the polymer composition.

[0016] According to an additional aspect of the invention a method ofembolizing a vascular site such as an aneurysm with a liquid emboliccomposition includes the steps of inserting a multiple lumen catheterendovascularly to a vascular site, injecting a liquid emboliccomposition through a first lumen of the multiple lumen catheter at thevascular site, and controlling solidification of the liquid emboliccomposition within the vascular site by injecting a solidification agentthrough a second lumen of the multiple lumen catheter at the vascularsite.

[0017] In accordance with a further aspect of the present invention, amethod for reducing toxic effects of a non-aqueous solvent deliveredintravascularly includes positioning a multi-lumen catheter into avascular site of a mammal, injecting a composition comprising anon-aqueous solvent through a first lumen of the multiple lumen catheterat the vascular site, and injection an aqueous solution through at leasta second lumen of the multiple lumen catheter at the vascular site todilute the non-aqueous solvent and reduce toxic effects of thenon-aqueous solvent on surrounding tissue.

[0018] In accordance with another aspect of the present invention, a kitfor controlled delivery in vivo of a liquid embolic composition includesa liquid embolic composition, and a multiple lumen catheter for deliveryof liquid embolic composition through a first lumen and delivery of asolidification agent through a second lumen.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The invention will be described in greater detail with referenceto the accompanying drawings in which like elements bear like referencenumbers, and wherein:

[0020]FIG. 1 is a side view of the catheter system according to thepresent invention;

[0021]FIG. 2 is an exploded side view of the catheter system of FIG. 1;

[0022]FIG. 3 is an enlarged cross-sectional view of the multiple lumencatheter taken along line 3-3 of FIG. 1;

[0023]FIG. 4 is an enlarged cross-sectional view of the multiple lumencatheter taken along line 4-4 of FIG. 1;

[0024]FIG. 5 is an enlarged cross-sectional view of the multiple lumencatheter taken along line 5-5 of FIG. 1;

[0025]FIG. 6 is an enlarged side cross-sectional view of an aneurysmbeing treated by the method according to the present invention;

[0026]FIG. 7 is an enlarged side cross-sectional view of an aneurysmshowing the detachment of an embolic mass from the catheter;

[0027]FIG. 8 is an enlarged perspective view of a distal end of acatheter according to a first alternative embodiment of the invention;

[0028]FIG. 9 is an enlarged perspective view of a distal end of acatheter according to a second alternative embodiment of the invention;

[0029]FIG. 10 is an enlarged cross-sectional view of the distal end of acatheter according to a third alternative embodiment of the invention;and

[0030]FIG. 11 is an enlarged cross-sectional view of a distal end of acatheter according to a fourth alternative embodiment of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0031] The catheter system of FIG. 1 includes a catheter having at leasttwo lumens for delivery of a liquid embolic composition through a firstlumen and delivery of a solidification agent through a second lumen. Theliquid embolic composition and the solidification agent are delivered tothe two lumens through a catheter connector which allows adjustment ofthe relative longitudinal positions of the two lumens. The cathetersystem is used to embolize vascular sites by controlled solidificationof the embolic composition within such sites.

[0032] The catheter system 10 includes an inner tube 12, an outer tube14, and proximal end connector 16 also called a Y-connector or Y-fittingfor connection of fluid supplies to the inner and outer tubes. The outertube 14 is positioned coaxially around the inner tube 12 forming anannular lumen between the inner and outer tubes and an annular outlet ofthe outer tube. The inner tube 12 is movable within the outer tube 14 byan actuator 18 and can be locked in place with respect to the outer tubeby a locking mechanism 20.

[0033] The method according to the present invention involves theinsertion of the multiple lumen catheter of the catheter system 10endovascularly to a vascular site such as an aneurysm and injecting aliquid embolic composition through a first lumen while injecting asolidification agent through a second lumen to control solidification ofthe liquid embolic composition. The controlled solidification of theliquid embolic composition allows the vascular site to be filled moreprecisely and rapidly, even when the aneurysm is located such thatgravity does not cause the liquid embolic to remain in such sites.

[0034] Prior to discussing the present invention in further detail, thefollowing terms are defined:

[0035] The term “embolic composition” refers to a fluid composition thatis injected into a blood vessel and solidifies to fully or partiallyocclude the vascular site.

[0036] The term “embolizing” or “embolization” refers to a processwherein a fluid composition is injected into a blood vessel which, inthe case of, for example, aneurysms, fills or plugs the aneurysm sacand/or encourages clot formation so that blood flow into the aneurysmand pressure in the aneurysm ceases, and in the case of arterial venousmalformations (AVMs) and arterial venous fistula (AVFs) forms a plug orclot to control/reroute blood flow to permit proper tissue perfusion.Embolization may be used for preventing/controlling bleeding due tolesions (e.g., organ bleeding, gastrointestinal bleeding, vascularbleeding, as well as bleeding associated with an aneurysm). In addition,embolization can be used to ablate diseased tissue (e.g., tumors, etc.)by cutting off its blood supply.

[0037] The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic, chemically inert, and substantiallynon-immunogenic when used internally in the patient and which aresubstantially insoluble in blood and other aqueous solutions but aresoluble in the fluid composition to the degree necessary to form a solidmass in vivo.

[0038] The term “contrast agent” refers to both water insoluble andaqueous based contrast agents which are visible by x-ray, fluoroscopy,CT scan, MRI, or the like.

[0039] The term “biocompatible solvent” refers to solvents capable ofdissolving the selected biocompatible polymer which are miscible orsoluble in aqueous compositions (e.g., blood). Suitable biocompatiblesolvents include ethanol, dimethylsulfoxide (DMSO), ethyl lactate,acetone, and the like as well as aqueous mixtures thereof having no morethan about 30 percent water. When employed at this level, the amount ofwater is sufficiently small that the dissolved polymer precipitates uponcontact with the blood. Preferably, the biocompatible solvent isanhydrous and, even more preferably, the biocompatible solvent isanhydrous dimethylsulfoxide (DMSO).

[0040] The term “solidification agent” refers to a liquid compositionwhich when in proximity to the liquid embolic composition, increases therate at which the liquid embolic composition solidifies. Examples ofsuch solidification agents include sterile water, sterile saline,Dextrose 5% water (D5W), lactated Ringers solution, contrast agents andthe like.

[0041] The term “catheter” includes both catheters and microcatheters.The catheters and microcatheters are designed for use in the highlytortuous blood vessels of the body, such as, intracranial blood vessels.By highly tortuous, we mean the typical tortuosity encountered in thevascular pathway from a remote access site such as the femoral artery totarget sites deep within in the coronary, renal, and cerebralvasculature. Specific embodiments may be constructed for access intotarget sites involving pathologically tortuous blood vessels, and bypathological tortuosity, we mean that the vascular pathway from a remoteaccess site such as the femoral artery to target sites involves turns inexcess of 90° when branching off from one blood vessel to another bloodvessel (paths which branch off the proceeding vessel at angles greaterthan a right angle), and where the total path length within the targettissue is at least about 5 cm and is also characterized as beingaccessible by a guidewire 0.018 inches or smaller, but being toodelicate and/or tortuous for accessing by a significantly largerdiameter guidewire.

[0042]FIGS. 1 and 2 illustrate the catheter system 10 according to thepresent invention through which the liquid embolic composition and thesolidification agent are injected into a vascular site to achievecontrolled solidification of the liquid embolic composition within theblood vessel. As illustrated in the exploded view of FIG. 2, a proximalend of the inner tube 12 extends through a rigid tube 22 whichstabilizes the proximal end of the inner tube. The proximal ends of therigid tube 22 and the inner tube 12 are connected to the actuator 18.The actuator 18 is positioned on a first luer hub 24 and includes asubstantially flat rectangular manipulator which is grasped by thephysician to move the inner tube 12 longitudinally within the outer tube14. The rigid tube 22 is positioned within the connector 16 with a stop26 of the rigid tube arranged between corresponding first and secondstops 28, 30 within the connector 16. The first and second stops 28, 30of the connector 16 engage the stop 26 of the rigid tube 22 to limit thelongitudinal motion of the inner tube 12 with respect to the outer tube14.

[0043] According to an alternative embodiment, proximal motion of theactuator 18 and the inner tube 12 is limited by engagement of the stop26 with the second stop 30. Distal motion of the inner tube 12 withrespect to the outer tube 14 is limited by engagement of the actuator 18with the locking mechanism 20.

[0044] The first luer hub 24 is positioned proximally of the actuator 18and provides mating means for mating with a syringe (not shown) filledwith the liquid embolic composition. A preferred luer hub/syringecombination is illustrated in U.S. patent application Ser. No.08/866,208 which is incorporated herein by reference in its entirety.Although the liquid embolic composition would generally be delivered tothe catheter by a syringe in a quantity which may be continuouslycontrolled by the physician, it may also be injected by other means suchas a high pressure injector or pump.

[0045] The catheter connector 16 includes a Y-arm 32 with a second luerhub 34 which provides mating means for mating with a supply of thesolidification agent. The Y-arm 32 extends from a side of the main bodyof the connector 16 for delivery of the solidification agent to theinterior of the connector. From the interior of the connector 16 thesolidification agent passes into the annular lumen between the outertube 14 and the inner tube 12. The outer tube 14 is connected to theconnector 16 by a distal end cap 46 of the connector. The outer tube 14may be connected by a compression fit by trapping the proximal end ofthe tube between the connector 16 and the end cap 46 by a threadedconnection. The outer tube 14 may also be connected to the connector byadhesive bonding, insert molding, and the like. The solidification agentmay be delivered to the outer tube 14 through the Y-arm 32 from avariety of sources, such as, a gravity feed saline bag, a pump, a highpressure injector, or a syringe.

[0046] An anti-kinking feature of the present invention is provided toprevent kinking of the inner tube 12 as it is pushed distally within theouter tube 14. The anti-kinking feature includes an outer rigid tube 48which is press fit within the stop 28. The stop 28 is in turn press fitwithin the main body of the connector 16. The inner rigid tube 22 slideswithin the somewhat larger outer rigid tube 48 to guide the inner tube12 within the outer tube 14 without kinking. When the inner rigid tube22 has been moved proximally until the stop 26 of the rigid tube engagesthe stop 30, an end of the inner rigid tube remains inside the outerrigid tube 48. Without the rigid tubes 22, 48, it would not be possibleto slide the inner tube 12 into the outer tube 14 because the flexibleinner tube would fold up within the connector 16.

[0047] The outer rigid tube 48 extends from the stop 28 toward thedistal end cap 46. However, the outer rigid tube 48 ends before aproximal end of the outer tube 14 providing a gap. Accordingly, thefluid injected through the luer hub 34 passes around the outer rigidtube 48, through the gap between outer rigid tube and the outer tube 14,and into the outer tube.

[0048] The locking mechanism 20 for locking the relative longitudinalpositions of the inner tube 12 and the outer tube 14 is best shown inthe exploded view of FIG. 2. The locking mechanism 20 includes anexternally threaded end 36 of the connector 16, a rotatable cap 38having internal threads, and a resilient sealing member 40. When theconnector 16 is assembled with the inner tube 12 positioned within theouter tube 14 the sealing member 40 is positioned around the rigid tube22 connected to the inner catheter tube 12. The sealing member 40 has ashape which includes an annular tapered surface at each end and athrough bore for receiving the rigid tube 22. The opposite annulartapered surfaces of the sealing member 40 engage correspondingly taperedsurfaces 42, 44 inside the connector 16 and inside a distal end of therotatable cap 38, respectively. In a preferred embodiment of the presentinvention, the sealing member 40 is a type of seal called a Tuohy-Borstseal.

[0049] The rigid tube 22 is placed inside the connector 16 such that theinner tube 12 is slidable within the outer tube 14, and the rigid tube22 is slidable within the connector and the rigid tube 48. As therotatable cap 38 is tightened onto the threaded end 36 of the connector16 the sealing member 40 is compressed between the tapered internalsurface 42 of the connector 16 and the tapered internal surface 44 ofthe cap. As the sealing member 40 is compressed longitudinally itexpands radially inwardly and radially outwardly to lock the rigid tube22 in place within the connector 16 and to provide a fluid tight sealbetween the interior surfaces of the connector and the exterior surfaceof the rigid tube. In this manner, the locking mechanism 20 freezes theends of the inner and outer tubes 12, 14 with respect to each other.

[0050] The inner and outer tubes 12, 14 for use in the present inventionare particularly designed to have sufficient rigidity to be insertedwith or without a guide wire to a location within a blood vessel forembolization and to have sufficient flexibility at the distal end toprevent damage to tissue. In order to achieve these objectives, ofrigidity at the proximal end and flexibility at the distal end, theinner and outer tubes 12, 14 may each be formed of two segments ofdiffering flexibilities joined together. The joints between the distaland proximal segments of the inner and outer tubes are longitudinallystaggered resulting in the three different cross sections of thecatheter illustrated in FIGS. 3-5. Although the invention is describedas employing catheter segments joined by joints, the catheter segmentsof differing cross-sections and flexibilities may be extruded togetheras a single piece to avoid the need for joints. Alternatively, the innerand outer tubes 12, 14 may have a continuously changing flexibilityalong their lengths.

[0051] As shown in FIG. 3, a proximal segment 12 a of the inner tube 12is formed of a material having a preferred durometer of approximately 40Shore D to 90 Shore D, more preferably approximately 60 Shore D to 80Shore D, and a diameter D1. A proximal segment 14 a of the outer tube 14is formed of a material having a preferred durometer of approximately 40Shore D to 90 Shore D, more preferably approximately 60 Shore D to 80Shore D, and a diameter D2.

[0052] The proximal segment 14 a of the outer tube 14 having thediameter D2 is fused to a distal segment 14 b of the outer tube whichhas a smaller diameter D3, shown in FIG. 4. The distal segment 14 b ofthe outer tube 14 has a durometer which is smaller than that of theproximal segment 14 a. Preferably, the durometer of the distal segment14 b is approximately 40 Shore A to 45 Shore D more preferablyapproximately 80 Shore A to 100 Shore A. The transition between thesegments 14 a, 14 b of the outer tube 14 occurs between the section line3-3 and the section line 4-4 in FIG. 1. This transition between thedistal and proximal segments 14 a, 14 b of the outer tube 14 is locatedalong the length of the catheter as required to allow the catheter to betracked along a tortuous path, preferably the transition is between 15and 20 cm from the distal end of the catheter.

[0053] The proximal segment 12 a of the inner tube 12 is fused to adistal segment 12 b of the inner tube, shown in FIG. 5. The proximal anddistal segments 12 a, 12 b of the inner tube preferably have the samediameter D1 but are formed of different materials with differentflexibilities. The distal segment 12 b of the inner tube 12 preferablyhas a durometer of approximately 40 Shore A to 45 Shore D, morepreferably approximately 80 Shore A to 100 Shore A.

[0054] One example of a multiple lumen catheter employed in the presentinvention has a usable length of about 150 cm, a proximal portion of theouter tube which is about 3.6 French and a distal portion of the outertube which is about 2.6 French. The wall thicknesses of the inner andouter tubes vary from about 0.003 inches (0.008 cm) to about 0.005inches (0.013 cm), with the proximal portion of the outer tube havingthe largest wall thickness. The proximal portions of the inner and outertubes are formed of high density polyethylene having a durometer ofabout 70 Shore D. The more flexible distal portions of the inner andouter tubes are formed of about 40% low density polyethylene and about60% Engage by Dow. (polyolefin) having a durometer of about 35 Shore D.This catheter configuration has been described only as an-example.

[0055] Catheters having a size of between about 1.5 and 5.0 French maybe used for treatment of aneurysms and other sizes may also be used forother types of treatments of vascular sites. The catheters may also bebraided or coil reinforced and formed of a wide variety of materials.Braided or otherwise reinforced catheters provide kink resistance, crushresistance, and steerability.

[0056] The inner tube 12 is movable from an extended position in whichthe inner tube extends from the distal end of the outer tube 14 by up toabout 30 mm to a retracted position in which the inner tube distal endis even with or inside the distal end of the outer tube 14. Movement ofthe actuator 18 in the direction of arrow A in FIG. 1 provides acorresponding movement of the distal end of the inner tube 12 in thedirection of the arrow B. The inner and outer tubes 12, 14 preferablyexperience minimal elongation or compression such that the distance oftravel of the actuator 18 is substantially the same as the distance oftravel of the distal end of the inner tube 12.

[0057] The tip of the catheter is preferably shaped prior to use by thephysician to a desired shape for the particular location andconfiguration of the vasculature to be treated. The tip of the catheteris shaped by placing a tip shaping mandrel in the lumen of the innertube 12. A sleeve may also be placed in the lumen between the outer tube14 and the inner tube 12 during shaping to support the outer tube. Thecatheter tip with the mandrel and the sleeve is then shaped to a desiredcurvature by the physician and subsequently steam heated to hold thecurvature once the mandrel and sleeve have been withdrawn.

[0058] The method according to the present invention involves theinjection of a solidification agent to control the solidification of theembolic composition within a blood vessel. The solidification agentallows for rapid, controlled solidification of the embolic compositionand places more control of the embolization procedure in the hands ofthe physician.

[0059] One example of a liquid embolic composition for embolizinganeurysms includes a biocompatible, water insoluble polymer, a contrastagent, and a biocompatible solvent such as dimethylsulfoxide (DMSO).Examples of such embolizing compositions ate described in U.S. Pat. No.5,667,767, which issued Sep. 16, 1997, U.S. Pat. No. 5,580,568, whichissued on Dec. 3, 1996, and allowed U.S. patent application Ser. No.08/688,050 each of which are incorporated herein by reference in theirentirety.

[0060]FIG. 6 illustrates the use of the method and apparatus accordingto the present invention to occlude an aneurysm 70 having a relativelylarge neck 72 which has formed at a branch in a blood vessel 74. Theaneurysm 70 is treated by inserting the, multiple lumen catheter of FIG.1 endovascularly until a distal end of the catheter is positioned withinor near the aneurysm or the neck 72 of the aneurysm. The position of thecatheter tip will vary depending on the aneurysm shape, size, and flowpattern. A guide wire (not shown) positioned in the inner tube 12 may ormay not be used to guide the catheter through the blood vessels. Othermethods of tracking the catheter to the aneurysm include steerablesystems in which the catheter tip is steered, flow directed systems, orsheath directed systems in which the catheter is delivered through asheath. The insertion of the catheter is generally performed underfluoroscopic visualization in a known manner.

[0061] As shown in FIG. 6, the distal ends of the inner and outer tubes12, 14 each have a radiopaque marker 50, 52, respectively, to allow thephysician to view the relative positions of the distal ends of the twocatheter tubes and the position of the catheter tubes with respect tothe aneurysm 70. The radiopaque markers 50, 52 may be formed either atthe inner or outer diameters of the tubes 12, 14. While tracking thecatheter through a typical tortuous path, the inner tube 12 may beextended from the end of the outer tube 14 to improve the flexibilityand tracking of the catheter distal end.

[0062] Prior to delivery of the liquid embolic composition to theaneurysm 70, the lumen 62 of the inner tube 12 is preferably flushedwith a barrier fluid to remove any aqueous material, such as blood,saline, or contrast agent from the inner tube which may cause theembolic composition to solidify within the catheter and block thecatheter. The catheter does not need to be entirely primed with thebarrier fluid as long as the column of barrier fluid is of a sufficientlength to prevent contact between the liquid embolic composition and anyaqueous material in the catheter. The barrier fluid may be thebiocompatible solvent or another fluid providing a barrier betweenaqueous fluids and the liquid embolic composition.

[0063] High concentrations of organic solvents such as DMSO, ethanol andothers when used as barrier fluids can be toxic to tissue and may causevascular spasms. In order to avoid the high solvent concentrations whichare toxic to tissue, a dilution liquid is injected through the annularlumen 60 between the inner and outer tubes 12, 14 during injection ofthe barrier fluid. The dilution liquid may be the same liquid as thesolidification agent, e.g., saline, or may a different liquid.

[0064] The injection of a dilution agent minimizes the effect of thetoxicity of an organic solvent and greatly increases the solventinjection flow rate which can be used safely. Preferably, the dilutionagent is injected through the lumen 60 of the outer tube 14 before or assoon as the solvent begins to exit the inner lumen 62 before any of theembolic composition has been injected. The dilution agent causes thesolvent to diffuse in the vessel treatment area at a much higher rate,and therefore, the concentration of the solvent in contact with thetissue is greatly decreased. A contrast agent may be used as thedilution agent to help visualize flow characteristics of the aneurysmand determine optimum catheter placement within the aneurysm.

[0065] According to the method of the present invention illustrated inFIG. 6, the aneurysm 70 is treated by injection of the liquid emboliccomposition into the aneurysm 70 through the lumen 62 of the inner tube12 by a syringe or other delivery mechanism attached to the luerconnection 24. The solidification agent, e.g., saline, is injectedthrough the lumen 60 of the outer tube 14 in tandem or just subsequentto the injection of the liquid embolic composition. The solidificationagent may be injected in a continuous or a pulsatile manner. Thesolidification agent washes the area of the aneurysm of blood which hasbecome saturated with solvent, replacing it with fresh solidificationagent. The washing action of the solidification agent is used to removeblood and other viscous fluids in the aneurysm which are otherwisedifficult to displace. In addition, the solidification agent provides adiffusion bed of solidification agent and increases the diffusiongradient which improves the diffusion of the solvent from the emboliccomposition as the composition solidifies in a coherent mass.

[0066] Without the use of the solidification agent the solventconcentration gradient between the liquid embolic composition beinginjected and the surrounding blood decreases as the solvent dissipatesfrom the embolic composition slowing the rate at which the solventdiffuses from the embolic composition. The solidification agent is usedto increase the solvent concentration gradient which causes the solventdiffusion rate to increase.

[0067] According to an alternative embodiment of the invention, theliquid embolic composition and solidification agent are injectedalternately rather than simultaneously. The injection of liquid emboliccomposition alone will form a nearly spherical shape. The liquid embolicinjection may then be discontinued while the solidification agent isinjected to solidify the spherically shaped mass of liquid embolic. Thetiming of the injection of the liquid embolic composition and thesolidification agent may be varied to achieve different results.

[0068] The inner tube 12 is slidable within the outer tube 14 so thatthe tip of the inner tube can be extended to different lengths from thedistal end of the outer tube to further control the solidification ofthe embolic composition depending on the aneurysm size, shape, and flowcharacteristics. The injection of a fluid through the annulus betweenthe inner and outer tubes 12, 14 may also be used to aid in the movementof the inner tube inside the outer tube by creating a moving fluidcolumn which reduces friction between the tubes. The use of fluid as afriction reducing mechanism may be particularly useful when the catheterhas been tracked through a typically tortuous path such as that providedby the blood vessels of the brain.

[0069] When embolization of the aneurysm is completed or is halted forsome other reason, the outer tube 14 serves as a lip to disconnect theembolic mass from the catheter by retracting the inner tube 12 into theouter tube. The separation of a coherent solid mass of emboliccomposition E from the end of the catheter is illustrated in FIG. 7.Without the detachment mechanism provided by the movable inner tube 12,it may be difficult for the physician to separate the embolic mass Efrom the catheter without causing trauma to the surrounding tissue. Thedetachment may be provided by any one or more of the following steps: 1)retracting the inner tube 12 into the outer tube 14; 2) advancing theouter tube over the inner tube; or 3) injecting solidification agent todetach the embolic mass from the outer tube.

[0070] In order to visualize the flow in the area being treated,including the flow into and out of the aneurysm, the dilution agentand/or the solidification agent can be combined with a contrast agentand injected alone prior to injection of the liquid embolic composition.Further, washout can be visualized by injection of contrast agentthrough the inner lumen while solidification agent is injected throughthe annular -lumen between the inner and outer tubes 12, 14.

[0071] Although the present invention has been described as employing acoaxial catheter having coaxial lumens, the present invention may alsoemploy other types of multiple lumen catheters such as those shown inFIGS. 8-11. Additional multiple lumen catheter configurations other thanthose shown may also be used, including catheters having multiple lumensfor delivery of the liquid embolic composition and catheters havingmultiple lumens for delivery of the solidification agent. Further, twoindependent catheters may be used for separate delivery of the liquidembolic composition and the solidification agent to achieve thecontrolled solidification of the embolic composition according to themethod of the present invention.

[0072] A multiple lumen catheter 80 illustrated in FIG. 8 has a firstlumen 82 and a second lumen 84 positioned side by side. In this side byside embodiment, the liquid embolic composition is injected through thefirst lumen 82 while the solidification agent is injected through thesecond lumen 84.

[0073] As shown in FIG. 9, the outlets of the two lumens 82 a, 84 a maybe longitudinally staggered so that the solidification agent injectedthrough the second lumen 84 a washes around the outlet of the firstlumen 82 a delivering the embolic composition. In addition, theside-by-side embodiments of FIGS. 8 and 9 may include means foradjusting the longitudinal position of one of the lumens with respect tothe other lumen.

[0074]FIG. 10 illustrates another alternative embodiment of a multiplelumen catheter 90 having an inner tube 92 and an outer tube 94 coaxiallysurrounding the inner tube. The outer tube 94 includes a distal taperedportion,96 and a plurality of openings 98 or side holes. The liquidembolic composition is delivered through the inner tube 92 while thesolidification agent is delivered through the outer tube 94 and exitsboth and through end of the outer tube and through the openings 98. Thetapered portion 96 of the outer tube 94 causes the solidification agentto be injected at an increased velocity along the inner tube 92 andwashes the liquid embolic as it is injected from the inner tube. Thesize and number of the openings 98 and the degree of taper may be variedto provide different amounts of flow through the end of the outer tube94 and through the openings.

[0075]FIG. 11 illustrates a further alternative embodiment of a multiplelumen catheter 100 in which an outer coaxial tube 104 is fused to aninner coaxial tube 102 at a distal end of the catheter. One or moreopenings 106 or side holes are provided in a side wall of the outertube, 104 for delivery of the solidification agent. The openings 106 maybe particularly designed to deliver the solidification agent in adesired delivery pattern by variation of the number, size, and locationof the openings.

[0076] Although the present invention has been described in detail foruse in treatment of aneurysms, it can also be used in a variety of otherapplications where controlled solidification of a liquid emboliccomposition is desired. For example, the present invention may be usedto occlude a blood vessel in order to block the blood flow to a tumor toablate tumorous tissue. The present invention may be used to controlbleeding in blood vessels by occluding a blood vessel. Further, thepresent invention may be used to control the solidification of abiocompatible polymer which is used for reversible sterilization or forbulking of tissues to treat urinary incontinence.

[0077] The injection of the solidification agent to control thesolidification of the embolic composition according to the presentinvention is particularly useful in situations where high flow rates maycarry the liquid embolic away from the embolization site before it issolidified in a mass, for example an AVF, and for situations where theposition of the formation to be filled with the embolic composition doesnot allow the liquid embolic composition to remain by gravity in theformation. The invention may also be particularly useful in situationswhere the fluid flow is very low and the solvent is not carried away asit dissipates from the embolic composition.

[0078] The catheter for use in the present invention particularly theinner tube 12, and also the connector 16 and the actuator 18, are formedof solvent compatible materials. According to a preferred embodiment ofthe invention in which the solvent is DMSO, the catheter elements whichmay come into contact with the solvent are DMSO compatible. Examples ofDMSO compatible materials and some of the preferred durometers of thesematerials for use in a catheter include polyolefins, such as,polyethylene (80A-80D), polyester polyether block copolymer (30D-80D),Alcryn (chlorinated polyolefin) (60A-80A), Pebax (polyamide polyetherblock copolymer) (25D-70D); fluoropolymers, such as, PTFE (such asTeflon), ETFE, and SEBS (styrene ethylene butadiene styrene); silicones;interpenetrating networks of silicone; and nylons (6/6, 6/10, and 6/12);and polyimide.

[0079] The inner and outer tubes 12, 14 are preferably coated withlubricous coatings both on their inner and outer diameters. Inparticular, a lubricous coating on the outer diameter of the outer tube14 assists the insertion of the catheter, while lubricous coatings onthe inner diameter of the outer tube and on the outer diameter of theinner tube 12 improve the longitudinal motion of the inner tube withinthe outer tube. A lubricous coating on the inner diameter of the innertube 12 will improve guidewire movement within the catheter. Thelubricous coating on the inner diameter of the inner tube 12 should becompatible with the biocompatible solvent.

[0080] The inner and outer rigid tubes 22, 48 within the connector 16 ofthe present invention may also include a keyed slot extendingsubstantially along their lengths to prevent the relative rotation ofthe inner and outer tubes 12, 14 at their proximal end. For example, theinner rigid tube 22 may include an external longitudinal groove whichreceives an internal longitudinal rib of the outer rigid tube 48.

[0081] Suitable biocompatible polymers for-use in the liquid emboliccomposition of the present invention include, by way of example,non-biodegradable polymers such as cellulose acetates (includingcellulose diacetate), ethylene vinyl alcohol copolymers, hydrogels(e.g., acrylics), polyacrylonitrile, polyvinylacetate, cellulose acetatebutyrate, nitrocellulose, copolymers of urethane/carbonate, copolymersof styrene/maleic acid, and mixtures thereof. Other suitablebiocompatible polymers include, for example, biodegradable polymers suchas linear-chain polymers such as polylactides, polyglycolides,polycaprolactones, polyanhydrides, polyamides, polyurethanes,polyesteramides, polyorthoesters, polydioxanones, polyacetals,polyketals, polycarbonates, polyorthocarbonates, polyhydroxybutyrates,polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates,poly(malic acid), poly(amino acids), polyhydroxycellulose, chitin,chitosan, and copolymers, terpolymers and combinations thereof.

[0082] Preferably, the biocompatible polymer does not cause adverseinflammatory reactions when employed in vivo.

[0083] The particular biocompatible polymer employed is selectedrelative to the viscosity of the resulting polymer solution, thesolubility of the biocompatible polymer in the biocompatible solvent,and the like. Such factors are well within the skill of the art.

[0084] Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer. Cellulose diacetate polymers areeither commercially available or can be prepared by art recognizedprocedures. In a preferred embodiment, the number average molecularweight, as determined by gel permeation chromatography, of the cellulosediacetate composition is from about 25,000 to about 100,000 morepreferably from about 50,000 to about 75,000 and still more preferablyfrom about 58,000 to 64,000. The weight average molecular weight of thecellulose diacetate composition, as determined by gel permeationchromatography, is preferably from about 50,000 to 200,000 and morepreferably from about 100,000 to about 180,000. As is apparent to oneskilled in the art, with all other factors being equal, cellulosediacetate polymers having a lower molecular weight will impart a lowerviscosity to the composition as compared to higher molecular weightpolymers. Accordingly, adjustment of the viscosity of the compositioncan be readily achieved by mere adjustment of the molecular weight ofthe polymer composition.

[0085] Ethylene vinyl alcohol copolymers comprise residues of bothethylene and vinyl alcohol monomers. Small amounts (e.g., less than 5mole percent) of additional monomers can be included in the polymerstructure or grafted thereon provided such additional monomers do notalter the embolizing properties of the composition. Such additionalmonomers include, by way of example only, maleic anhydride, styrene,propylene, acrylic acid, vinyl acetate and the like.

[0086] Ethylene vinyl alcohol copolymers are either commerciallyavailable or can be prepared by art recognized procedures. Preferably,the ethylene vinyl alcohol copolymer composition is selected such that asolution of 6 weight percent of the ethylene vinyl alcohol copolymer, 25weight percent of a tantalum contrast agent in DMSO has a viscosityequal to or less than 60 centipoise at 20° C. As is apparent to oneskilled in the art, with all other factors being equal, copolymershaving a lower molecular weight will impart a lower viscosity to thecomposition as compared to higher molecular weight copolymers.Accordingly, adjustment of the viscosity of the composition as necessaryfor catheter delivery can be readily achieved by mere adjustment of themolecular weight of the copolymer composition.

[0087] As is also apparent, the ratio of ethylene to vinyl alcohol inthe copolymer affects the overall hydrophobicity/hydrophilicity of thecomposition which, in turn, affects the relative watersolubility/insolubility of the composition as well as the rate ofprecipitation of the copolymer in an aqueous solution (e.g., blood). Ina particularly preferred embodiment, the copolymers employed hereincomprise a mole percent of ethylene of from about 25 to about 60 and amole percent of vinyl alcohol of from about 40 to about 75. Thesecompositions provide for requisite precipitation rates suitable for usein embolizing blood vessels.

[0088] While the invention has been described in detail with referenceto a preferred embodiment thereof, it will be apparent to one skilled inthe art that various changes and modifications can be made, andequivalents employed, without departing from the spirit and scope of theinvention.

What is claimed is:
 1. A catheter system for controlling solidificationin vivo of liquid embolic compositions which catheter system comprises:(a) a multiple lumen catheter having a first lumen and a second lumenfor delivery of fluid; (b) a first fluid delivery port for delivery offluid to the first lumen; (c) a second fluid delivery port for deliveryof fluid to the second lumen; (d) a liquid supply connected to the firstfluid delivery port for delivery of a liquid embolic composition throughthe first lumen; and (e) a solidification agent supply connected to thesecond fluid delivery port for delivery of a solidification agentthrough the second lumen to enhance solidification of the liquid emboliccomposition when delivered in vivo through the first lumen.
 2. Thecatheter system according to claim 1, wherein the multiple lumencatheter includes an inner tube and an outer tube coaxially surroundingthe inner tube.
 3. The catheter system according to claim 2, wherein theinner tube is longitudinally movable within the outer tube to adjust arelative position of an outlet of the inner tube with respect to anoutlet of the outer tube.
 4. The catheter system according to claim 3,further comprising a locking mechanism for locking a position of theinner tube with respect to the outer tube.
 5. The catheter systemaccording to claim 3, wherein the relative positions of the inner tubeand the outer tube are movable from a first position in which the innertube extends from the outlet of the outer tube, to a second position inwhich the outlet of the inner tube is positioned within the lumen of theouter tube, wherein the relative motion of the inner and outer tubesfrom the first position to the second position detaches a solidifiedmass of the embolic composition from the multiple lumen catheter.
 6. Thecatheter system according to claim 1, wherein an outlet of the firstlumen and an outlet of the second lumen of the multiple lumen catheterare longitudinally movable with respect to one another to changerelative longitudinal positions of the outlets of the first and secondlumens to control solidification of the liquid embolic composition. 7.The catheter system according to claim 1, wherein the liquid emboliccomposition comprises a water-insoluble, biocompatible polymer dissolvedin a biocompatible solvent and the catheter is compatible with thebiocompatible solvent.
 8. The catheter system according to claim 7,wherein the biocompatible solvent is DMSO.
 9. The catheter systemaccording to claim 8, wherein the multiple lumen catheter is DMSOcompatible.
 10. The catheter system according to claim 1, wherein thebiocompatible polymer is water insoluble and the solidification agent isselected from the group consisting of water, saline, Dextrose 5% water,lactated Ringers solution, and aqueous based contrast agents.
 11. Acatheter for controlling solidification in vivo of liquid emboliccompositions comprising: (a) a first tube formed of a DMSO compatiblematerial; (b) a second tube connected to the first tube; (c) an actuatorfor sliding the first tube longitudinally with respect to the secondtube; (d) a first fluid delivery port connected to a lumen of the firsttube for delivery of a liquid embolic composition which compositioncomprises a biocompatible, water-insoluble polymer dissolved in DMSO,the first delivery port formed of a DMSO compatible material; and (e) asecond fluid delivery port connected to a lumen of the second tube fordelivery of a solidification agent which encourages solidification ofthe liquid embolic composition.
 12. The catheter according to claim 11,further comprising a locking mechanism for locking a longitudinalposition of the first tube with respect to the second tube.
 13. Thecatheter according to claim 11, wherein the second tube coaxiallysurrounds the first tube.
 14. The catheter according to claim 13,further comprising an anti-kinking mechanism for preventing kinking ofthe first tube as it slides in the second tube, the anti-kinkingmechanism including a rigid tube connected to the first tube andslidable within a sleeve.
 15. The catheter according to claim 13,wherein a distal end of the second tube includes a plurality of sideholes for delivery of the solidification agent.
 16. The catheteraccording to claim 11, wherein the first and second tubes each have aproximal portion with a durometer of between about 40 Shore D and 90Shore D.
 17. The catheter according to claim 16, wherein the first andsecond tubes each have a distal portion with a durometer of betweenabout 40 Shore A and 45 Shore D.
 18. The catheter according to claim 17,wherein a joint between the distal and proximal portions of the firsttube is longitudinally displaced from a joint between the distal andproximal portions of the second tube at all relative positions of thecatheter which are achieved by manipulation of the actuator.
 19. Amethod of treating aneurysms with a liquid embolic compositioncomprising: inserting a multiple lumen catheter endovascularly to ananeurysm site; injecting a liquid embolic composition through a firstlumen of the multiple lumen catheter at the aneurysm site; andcontrolling the solidification of the liquid embolic composition withinthe aneurysm by injecting a solidification agent through a second lumenof the multiple lumen catheter at the aneurysm site.
 20. The method oftreating aneurysms according to claim 19, wherein the multiple lumencatheter is a coaxial catheter and the solidification agent is injectedthrough an annulus between an inner and outer tube of the coaxialcatheter.
 21. The method of treating aneurysms according to claim 19,wherein an outlet the first lumen and an outlet of the second lumen ofthe multiple lumen catheter are longitudinally movable with respect toone another.22.
 22. The method of treating aneurysms according to claim21, wherein the liquid embolic composition and the solidification agentare injected when the outlets of the first and second lumens arelongitudinally spaced with respect to each other.
 23. The method oftreating aneurysms according to claim 22, wherein the outlets of thefirst and second lumens of the multiple lumen catheter are manipulatedwith respect to one another to detach a solidified mass of emboliccomposition from the multiple lumen catheter.
 24. The method of treatinganeurysms according to claim 21, wherein a fluid is injected through oneof the first and second lumens to improve longitudinal motion of theoutlets of the first and second lumens with respect to one another. 25.The method of treating aneurysms according to claim 19, wherein theinjected liquid embolic composition includes a biocompatible polymercomposition dissolved in a solvent.
 26. The method of treating aneurysmsaccording to claim 25, wherein the first lumen is flushed-with a barrierfluid prior to injection of the liquid embolic composition to preventaqueous fluids in the first lumen from coming into contact with theliquid embolic composition passing through the first lumen.
 27. Themethod of treating aneurysms according to claim 26, wherein the barrierfluid includes the solvent.
 28. The method of treating aneurysmsaccording to claim 27, wherein the solidification agent is injectedthrough the second lumen during the flushing of the first lumen with thebarrier fluid to lower a concentration of the solvent being delivered tothe patient.
 29. The method of treating aneurysms according to claim 19,wherein the liquid embolic composition and the solidification agent areinjected at the same time.
 30. The method of treating aneurysmsaccording to claim 19, wherein the liquid embolic composition and thesolidification agent are injected alternately.
 31. A method for reducingtoxic effects of a non-aqueous solvent delivered intravascularly whichmethod comprises: positioning a multiple lumen catheter into a vascularsite of a mammal; injecting a composition comprising a non-aqueoussolvent through a first lumen of the multiple lumen catheter at thevascular site; and injecting an aqueous solution through at least asecond lumen of the multiple lumen catheter at the vascular site todilute the non-aqueous solvent and reduce toxic effects of thenon-aqueous,-solvent on surrounding tissue.
 32. The method for reducingtoxic effects of a non-aqueous solvent according to claim 31, whereinthe non-aqueous solvent is DMSO.
 33. A kit for controlled delivery invivo of a liquid embolic composition comprising; a liquid emboliccomposition; and a multiple lumen catheter for delivery of the liquidembolic composition through a first lumen and delivery of asolidification agent through a second lumen.
 34. The kit according toclaim 33, wherein the multiple lumen catheter includes an inner tubelongitudinally movable within a coaxial outer tube.
 35. The kitaccording to claim 34, wherein the multiple lumen catheter furthercomprises a connector introducing the liquid embolic composition and thesolidification agent to the first and second lumens, the connectorincluding an anti-kinking mechanism allowing the inner tube to movewithin the outer tube without kinking.